The North

Our research in The North spans Newcastle, Leeds, Liverpool, Manchester, Sheffield and York.

We are looking for ways to improve the outcomes of people with AML, and testing for a new form of therapy for people with GvHD. And we are funding one of the best leukaemia genetics research resources in the world, which is transforming the way we treat children with leukaemia.

A number of clinical trials are taking place, that want to find out the best treatment for people with post-transplant lymphoproliferative disorders (PTLD), and we have a number of TAP trials that are finding new ways to treat people with chronic lymphocytic leukaemia (CLL) and Hodgkin lymphoma. We are also supporting a clinical trial that wants to see if people with chronic myeloid leukaemia (CML) are being over-treated, and if so, can they safely reduce their dose, or stop taking their medication completely.

Our researchers are searching for new ways to treat myeloma whilst combating the devastating bone destruction seen with this disease. We are also looking at targeting the signalling pathways that lymphoma needs to survive, which could lead to new treatment options for diffuse large B cell lymphoma (DLBCL).

The Haematological Malignancy Research Network (HMRN) is gathering detailed information about people with blood cancer in Yorkshire. This unique project is allowing researchers and doctors to gain a better understanding of how blood cancer can be treated and diagnosed.

Newcastle University

Research at Newcastle University is looking for ways to improve the outcomes of people with acute myeloid leukaemia (AML) by matching the treatment to the individual. We are also testing to see if using cytokines could be effective in treating people with Graft versus Host Disease (GvHD) who are no longer responding to conventional treatment. And we are creating a detailed picture of what starts and drives leukaemia, and which genes can be targeted by treatments.

One of the most aggressive blood cancers is AML, and it is often fatal within a year of diagnosis. People are with AML are usually given chemotherapy. But this treatment approach is not suitable for everyone. AML mainly affects the elderly, so many are unable to tolerate standard chemotherapy because they are too frail, or have other underlying conditions. And although chemotherapy can work well for many people, others will unfortunately see their AML return after treatment, and stem cell transplant is the only other option. Dr James Allan wants to develop new treatment options for people AML by matching existing therapies to the individual person so treatment has more success. The team will identify gene changes that influence clinical outcome, treatment resistance, and relapse, and will find ways to sensitise leukaemia cells to therapy. This ‘stratified medicine’ approach will improve risk prediction, identify potential new ways to target AML, and will find ways to reduce the chance of relapse.

A complication that can arise from stem cell transplants is Graft versus Host Disease (GvHD), which in severe cases can cause extensive tissue and organ damage. People who have GvHD are usually given drugs that suppress the immune system. But this course of treatment does not always work for everyone, so researchers are looking for new ways to treat GvHD. Professor Matthew Collin and his team want to see if using cytokines can help people with GvHD. Cytokines are groups of proteins that act as cell signalling molecules, allowing cells to communicate with each other when generating immune responses. IL-22 is a cytokine that is produced by immune cells in inflamed tissues, and may offer protection and help repair tissue damage caused by the immune response. The team will investigate if IL-22 could have a therapeutic use for people with GVHD.

One of our major childhood leukaemia projects are based at Newcastle University. Led by Professors Christine Harrison and Anthony Moorman, The Leukaemia Research Cytogenetics Group Specialist Programme is collaborating with scientists in the UK and across the globe to identify the genetic faults that drive leukaemia and cause treatment resistance.

In cancer, rearrangements occur between and within chromosomes, which contain tightly packed DNA. Cytogenetics looks at these changes in chromosomes, which can not only indicate the type of leukaemia someone has, but can also be used to predict the outcome of disease. Over the last 20 years, the group has established a cytogenetics resource for acute leukaemia (ALL and AML) that is now renowned as one of the best leukaemia genetics research resources in the world, and their work has transformed the way we treat children with leukaemia in the UK and beyond. The work of the laboratory contributes significantly to continuous improvement of the management of childhood leukaemia by improving how we diagnose leukaemia, predict response to treatments, detect when blood cancer is in remission or returning.

Newcastle upon Tyne Hospitals

We have a clinical trial that wants to find out the best treatment for post-transplant lymphoproliferative disorders (PTLD). These are lymphomas that can develop in people who are taking drugs that dampen down the immune system to prevent rejection of an organ or stem cell transplant. Currently, people with PTLD are treated with a biological drug called rituximab, and if they do not respond adequately after 7 weeks, receive additional treatment with a chemotherapy regime called R-CHOP. Although this strategy is often successful, many people do not respond or relapse. People receiving R-CHOP are also at a higher risk of infection, and this treatment can also damage the transplanted organ. Dr Tobias Menne is leading a trial, which wants to see if adding a biological therapy called ibrutinib to chemotherapy may improve the response rate compared to standard treatment with rituximab and chemotherapy.

St James's University Hospital Leeds

Although chemotherapy and rituximab can help many people with CLL, not everyone will do well on these drugs, and some eventually relapse. At the moment bone marrow transplantation is the only true cure for CLL, but some people may not be able to undergo this treatment because they are too frail.

Professor Peter Hillmen is running a number of Trials Acceleration Programme (TAP) trials from The St James’ University Hospital in Leeds. These trials are focused on finding new ways to treat people with chronic lymphocytic leukaemia (CLL) who are no longer responding to conventional chemotherapy, or who have relapsed.

The University of Liverpool

We are supporting the DESTINY clinical trial that wants to see if people with chronic myeloid leukaemia (CML) who are doing well on their tyrosine kinase inhibitors (TKIs) can safely reduce their dose, or stop taking the drugs altogether.

Most people with CML can now take drugs called TKIs as a single daily pill to control their CML. But some people can’t tolerate the side effects of TKIs, or become resistant to the drugs over time. So researchers want to find ways to improve the quality of life of people with CML who are taking these drugs. Professor Richard Clark is leading the DESTINY trial, which is investigating whether people who are responding well on their current TKI treatment for CML can remain well on either a lower dose of treatment or without treatment at all. This study will also help to develop a treatment decrease and stopping strategy for people who may develop CML in the future.

The University of Manchester

At the moment, we don’t have a lot of treatment options for AML, and it can be hard to treat, especially in older people who have a higher risk of developing the disease. Standard treatment is chemotherapy, and stem cell transplant is usually considered if chemotherapy fails or people relapse after initially responding to treatment.

Dr David Wiseman and his team are looking for new targeted ways to treat AML. One in five people with AML have a mutation in genes called isocitrate dehydrogenase 1 (IDH1) or IDH2. These leukaemias make an abnormal chemical called 2-hydroxyglutarate, which we think impairs how the body 'reads' other genes that control development of blood cells. Many people with AML also have changes in a gene called SRSF2, which in healthy cells plays a key role in processing the information from a gene into a protein. The team want to understand how these gene changes work together, and will test new drugs which target the mutated form of IDH1 to see if they kill leukaemia cells in the lab. If successful, they plan to test this further in clinical trials.

We are also supporting a TAP trial called BREVITY, which is looking at a new biologic treatment for people with Hodgkin lymphoma. People are usually treated with chemotherapy, but some are too frail, or have another medical condition which means they cannot have this treatment. Brentuximab vedotin has been shown to be effective for people whose Hodgkin lymphoma has come back after chemotherapy treatment, and Professor John Radford wants to see if this drug may also help people who are unable to tolerate standard chemotherapy. If successful, brentuximab vedotin could be used as a targeted first-line therapy for Hodgkin lymphoma, and may have fewer side effects than chemotherapy.

The University of Sheffield

Two major problems with myeloma are the devastating bone destruction often seen, and despite successful initial chemotherapy, myeloma comes back and ultimately causes death. Dr Andrew Chantry and his team are tackling these issues with two approaches. To combat the bone destruction caused by myeloma, researchers are combining a drug that helps to build bone up with another drug that prevents bone being removed from the body. The group hopes that this approach will provide protection to bone, and may lead for the first time to actually repairing the existing bone destruction. In the second part of Dr Chantry’s project, he wants to seek out the myeloma cells that are responsible for causing the blood cancer to return after treatment. The team wants to see if new combinations of recently available chemotherapies and new bone targeted drugs are able to destroy these cells.

University of Leeds

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma in the UK and is currently treated by chemotherapy together with an antibody therapy called rituximab. However, this approach is not always successful because many people do not respond, or only have a partial response. Much of our research in DLBCL is looking for new treatments, and targeting the signalling pathways that lymphoma needs to survive looks to be a promising option.

Healthy cells are tightly controlled by a complex communication network, which tells it when to divide, mature or die. Cancer can happen when these signalling pathways get disrupted, causing the cell to ignore the important signals that tell it to stop growing, or die. This may arise through genetic errors, which act as road blocks on the signalling network. But the cause of this disruption is still mainly unknown in lymphoma. Dr Reuban Tooze and his team now want to explore what is causing pathways to go awry, and to see if this is linked with other pathways that can drive lymphoma. Exploring these links could lead to new ways of treating lymphoma, and identify people who are most likely to benefit from drugs that target specific cancer-causing pathways.

University of York

We are supporting a project at The University of York called The Haematological Malignancy Research Network (HMRN). Dr Eve Roman and her team are gathering detailed information about people with blood cancer in Yorkshire, so researchers and doctors can gain a better understanding of how this disease can be treated and diagnosed.